The pyrimidine compound with which the present invention is concerned has the following structural formula ##STR1## and is known as buspirone. The hydrochloride salt has been referred to in the prior art as MJ 9022-1 and as buspirone hydrochloride. Other acid addition salts thereof are named by combining "buspirone" with the appropriate word to define the acid from which it is prepared as in "buspirone hydrochloride". The latter is the United States Adopted Name (USAN); refer to J. American Med. Assoc. 225, 520 (1973).
The synthesis of the compound and the disclosure of its psychotropic properties are described in the following patents and publications.
1. Y. H. Wu, et al., J. Med. Chem., 15, 477 (1972).
2. Y. H. Wu, et al., U.S. Pat. No. 3,717,634 which issued Feb. 20, 1973.
3. L. E. Allen, et al., Arzneium. Forsch., 24, No. 6, 917-922 (1974).
4. G. L. Sathananthan, et al., Current Therapeutic Research, 18/5, 701-705 (1975).
5. Y. H. Wu, et al., U.S. Pat. No. 3,976,776, issued Aug. 24, 1976.
The use of buspirone hydrochloride as a novel anti-anxiety agent for the treatment of neurotic patients is described in G. P. Casten, et al., U.S. Pat. No. 4,182,763, issued Jan. 9, 1980. Currently, a New Drug Application (NDA) is pending before the U.S. Food & Drug Administration for the use of buspirone in treatment of anxiety neurosis. In addition, other clinical studies are being conducted to lend support to the use of buspirone for the therapeutic method of the instant invention.
The present invention can be distinguished from the above prior art in that it is directed to a distinct patient population characterized by a disease state different from that related to the anxiolytic process disclosed in the prior art. Support for this distinction is found in the reference, "The Diagnostic Validity of Anxiety Disorders and Their Relationship to Depressive Illness", by A. Breier, et al., in Am. J. Psychiatry, 142:7 (July, 1985), pages 787-796. The diagnosis and treatment of panic disorders has been recently reviewed; cf: D. V. Sheehan, "Panic Attacks and Phobias", New England Journal of Medicine, 307, pages 156-158, 1982; R. I. Shader, et al., "Panic Disorders: Current Perspectives", J. Clin. Pyschopharmacology, 2/6 Supplement, pages 2S-26S, 1982; and W. Matuzas, et al., "Treatment of Agoraphobia and Panic Attacks", Arch. Gen. Psychiatry, 40, pages 220-222, 1983.
Although panic disorder is a relatively new diagnosis, the basic diagnostic concepts are well known to those skilled in the art and are clearly differentiated from generalized, persistent anxiety. Although the prior art references concerning buspirone disclose the compounds described in the instant application and their tranquilizing and anti-anxiety effects, none of these prior art buspirone references disclose or suggest that these compounds are useful to treat or prevent panic disorders which is the applicants' claimed invention.
An example for comparison which distinguishes use in generalized anxiety from use in panic disorder is the drug alprazolam which was disclosed in U.S. Pat. No. 3,987,052, issued October, 1976 to Hester as having sedative, tranquilizing and muscle relaxant effects and could be used to alleviate tension and anxiety in mammals. U.S. Pat. No. 4,508,726, issued April, 1985, to Coleman discloses and claims the treatment of panic disorders with alprazolam. Further, U.S. Pat. No. 4,508,726 admits that alprazolam had been previously disclosed for the management of anxiety disorders. Alprazolam, a benzodiazepine compound, bears no structural or biochemical relationship to buspirone and would not suggest its usefulness in panic disorders.
In summary, buspirone and its pharmaceutically acceptable salts bear no structural resemblance to any therapeutic agent alleged to be useful in the treatment of panic disorders. It is now appreciated by those skilled in the art that generalized anxiety and panic disorders are distinguishable disease states with differently defined patient populations. There also exists nothing in the prior art which teaches or suggests that the instant compounds would be useful in alleviation of panic disorder.